亚甲基四氢叶酸还原酶基因在氯氮平诱导代谢综合征中的作用

Effect of methylenetetrahydrofolate gene on metabolic syndrome induced by clozapine

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)在氯氮平诱导代谢综合征(MS)中的作用。 方法:根据《美国国家胆固醇教育项目成人治疗组第三次指南》(NCEP-ATPⅢ)标准,将服用氯氮平≥2年的576例患者分为MS组(n=246)和非MS组(n=330);测量入组者身体及糖脂生化指标;使用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术检测入组者MTHFR基因C677T位点基因型及等位基因频率,分析各基因型间的生化指标。结果:MS组体质量指数(BMI)、腰围、空腹血糖(GLU)、血清三酰甘油(TG)水平及血压显著高于非MS组,血清高密度脂蛋白(HDL)水平显著低于非MS组(P<0.05或P<0.01)。MS组C677T位点TT基因型及T等位基因频率显著高于非MS组(P<0.05或P<0.01);与TC及CC基因型比较,TT基因型患者BMI及GLU水平显著增高,HDL水平显著降低(F=12.14,F=4.62,F=7.64;P均<0.001)。 结论:MTHFR基因C677T位点多态性影响血浆同型半胱氨酸代谢,增加氯氮平诱导MS的风险。

Objective: To investigate the role of methylenetetrahydrofolate reductase (MTHFR) in clozapine-induced metabolic syndrome (MS). Method: According to the National Cholesterol Education Program Adult Treatment Group Third Guide (NCEP-ATPIII) criteria,576 patients taking clozapine≥2 years were divided into MS group ( n =246)and non-MS group( n =330).The body and glycolipids biochemical indexes of the participants were measured,and genotype and allele frequency of MTHFR gene C677T site were detected by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) technology.The biochemical indicators among the genotypes were compared and analyzed. Results: Body mass index (BMI),waist circumference,fasting blood glucose (GLU),serum triglyceride (TG) levels,and blood pressure in MS group were significantly higher than those in the non-MS group,and serum high-density lipoprotein (HDL) level in MS group was significantly lower than that in non-MS group( P <0.05 or P <0.01).The frequencies of TT genotype and T allele of the C677T site in the MS group were significantly higher than those in the non-MS group ( P <0.05 or P <0.01).Compared with the patients with TC and CC genotypes,BMI and GLU levels and decreased HDL levels in patients with TT genotype were significantly increased ( F=12.14,F=4.62,F=7.64;P < 0.001). Conclusion: The MTHFR gene C677T polymorphism affects plasma homocysteine metabolism and increases the risk of clozapine-induced MS.